Major histocompatibility complex (MHC) class I molecules are crucial for immune response, presenting peptide fragments of non-self proteins to cytotoxic T cells. They consist of an α-chain and β2-microglobulin, with recognition requiring cell contact and specific peptide-MHC association. If the MHC I molecules are absent, natural killer (NK) cells respond to potentially infected cells, indicating their role in cellular immunity.

2.  Major Histocompatibility Complex
 Cluster of genes found in all mammals
 Participant in both humoral and cell-mediated immunity
 Act as antigen presenting structures
 Polymorphic glycoproteins
MHC class I molecules are one of two primary classes of major
histocompatibility complex (MHC) molecules (the other being MHC
class II) and are found on the cell surface of all nucleated cells .

3. 1. MHC molecules are membrane-bound. Recognition by T cells
requires cell-cell contact.
2. Peptide from cytosol associates with class I MHC and is
recognized by Tc cells.
3. Although there is a high degree of polymorphism for a species,
an individual has maximum of six different class I MHC
products.

4. 4. A peptide must associate with a given MHC
of that individual, otherwise no immune
response can occur. That is first level of
control. Mature
T cells must have a T cell receptor that
recognizes the peptide associated with
MHC. This is the second level of control.

5. • Their function is to display peptide fragments of non-
self proteins from within the cell to cytotoxic T cells;
• This will trigger an immediate response from the
immune system against a particular non-self antigen
displayed with the help of an MHC class I protein.

6. 1
3
2
MHC-encoded -chain of 43kDa ,Made Up Of 3
Domains (1, 2 and 3)
2m
2-microglobulin, 12kDa, non-MHC encoded, non-
transmembrane, non covalently bound to 3 domain
The a3 segment of the MHC I , is highly conserved
among MHC1 & serves as a binding site for CD8
Peptide antigen in a groove formed from a pair of a-
helicies on a floor of anti-parallel b strands
-chain anchored to the cell membrane

8. • Conversion of native antigen (large globular protein) into peptides capable of
binding to MHC molecules
• Occurs in cellular compartments where MHC molecules are synthesized and
assembled (ER)
– Determines how antigen in different cellular compartments generates peptides
that are displayed by class I or class II MHC molecules

9. 1. Only fragments of proteins (peptides) associated with MHC
molecules on surface of cells
• Helper T cells CD4+(Th) recognize peptide associated with
MHC class II molecules
• Cytotoxic T cells CD8+ (Tcyt) recognize peptide associated
with MHC class I molecules.

10. Dendritic cells

18. The fate of the virus-infected cell is almost
always induction of apoptosis through cell-
mediated immunity , reducing the risk of
infecting neighboring cells.
Therefore, in the absence of MHC I molecules,
NK cells are activated and recognize the cell as
aberrant, suggesting that it may be infected by
viruses attempting to evade immune destruction.

19. Cellular and Molecular Immunology 8th Ed. (2015) by Abbas et al.
MHC I
Composed of an α (or heavy) chain in a non-covalent complex
with a β2- microglobulin
Recognized by CD8+ T cells
Expressed on all nucleated cells
Cytosolic proteins are proteolytically degraded in the
proteasome